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H Takada

Publications and source records attributed to H Takada.

At least 73 records · Page 4Linked to original sources
PubMed2001

Synergistic effect of muramyldipeptide with lipopolysaccharide or lipoteichoic acid to induce inflammatory cytokines in human monocytic cells in culture.

An analog of 1alpha,25-dihydroxyvitamin D3, 22-oxyacalcitriol (OCT), differentiated human monocytic THP-1 and U937 cells to express membrane CD14 and rendered the cells responsive to bacterial cell surface components. Both THP-1 and U937 cells expressed Toll-like receptor 4 (TLR4) on the cell surface and TLR4 mRNA in the cells, irrespective of OCT treatment. In contrast, OCT-treated U937 cells scarcely expressed TLR2 mRNA, while OCT-treated THP-1 cells expressed this transcript. Muramyldipeptide (MDP) by itself exhibited only a weak ability to induce secretion of inflammatory cytokines such as interleukin-8 (IL-8) in the OCT-differentiated THP-1 cells but showed marked synergistic effects with Salmonella lipopolysaccharide (LPS) or lipoteichoic acid (LTA) from Staphylococcus aureus, both of which exhibited strong activities. Combinatory stimulation with LPS plus LTA did not show a synergistic effect on OCT-differentiated THP-1 cells. Similar results were observed in OCT-differentiated U937 cells, although combination experiments were carried out only with MDP plus LPS. Anti-CD14 monoclonal antibody (MAb) MY4, anti-TLR4 MAb HTA125, and the synthetic lipid A precursor LA-14-PP almost completely inhibited the IL-8-inducing activities of LTA as well as LPS on OCT-treated THP-1 cells, but these treatments increased MDP activity. OCT-treated THP-1 cells primed with MDP exhibited enhanced production of IL-8 upon stimulation with LPS, while the cells primed with LPS showed no change in production upon stimulation with MDP. MDP up-regulated mRNA expression of an adapter molecule to TLRs, MyD88, to an extent similar to that for LPS in OCT-treated THP-1 cells. These findings suggested that LTA as well as LPS activated human monocytic cells in a CD14- and TLR4-dependent manner, whereas MDP exhibited activity in a CD14-, TLR4-, and probably TLR2-independent manner and exhibited synergistic and priming effects on the cells for cytokine production in response to various bacterial components.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed2001

Effects of superantigen and lipopolysaccharide on induction of CD80 through apoptosis of human monocytes.

To investigate the mechanisms underlying superantigen (SAg) stimulation, we analyzed the effect of SAg on monocyte responses with or without lipopolysaccharide (LPS). Addition of gamma interferon (IFN-gamma) to unstimulated cultures induced a marked increase in the number of CD80(+) monocytes, which was inhibited by LPS through the action of interleukin-10. However, CD80(+) monocytes began to increase before IFN-gamma production, observed after 9 h of stimulation with staphylococcal enterotoxin B (SEB). SEB selectively increased the number of apoptotic CD80(-) monocytes, whereas LPS-treated monocytes were resistant to the apoptotic action of SEB. This SEB-induced killing was abrogated by anti-CD95 monoclonal antibody (MAb) ZB4 and anti-CD95 ligand (CD95L) MAb NOK2, suggesting a CD95-based pathway of apoptosis. Furthermore, the numbers of SEB-induced CD80(+) monocytes were partially decreased by anti-CD119 (IFN-gamma receptor) MAb and by anti-CD95L (NOK2) MAb. The CD30 expression of CD27(high) T cells induced by SEB was increased by agonistic anti-CD95 (CH11) MAb. Together, our findings showed that SEB-induced monocyte apoptosis is closely associated with the enrichment of CD80(+) monocytes generated before IFN-gamma production, followed by up-regulation of CD80 by IFN-gamma, and that LPS has negative effects in both cases. These results also suggested that induction of monocyte apoptosis is an important mechanism by which SAg exerts its anti-inflammatory effects.

Apoptosis↗
PubMed2001

Monocytic cell activation by Nonendotoxic glycoprotein from Prevotella intermedia ATCC 25611 is mediated by toll-like receptor 2.

Lipopolysaccharide (LPS) preparations from gram-negative black-pigmented bacteria such as Porphyromonas gingivalis and Prevotella intermedia activate cells from non-LPS-responsive C3H/HeJ mice, but it is still unclear whether this activity is due to the unique structure of LPS or to a minor component(s) responsible for the activity in the preparation. A nonendotoxic glycoprotein with bioactivity against cells from C3H/HeJ mice was purified from a hot phenol-water extract of P. intermedia ATCC 25611 and designated Prevotella glycoprotein (PGP). Treatment of human monocytic THP-1 cells with 22-oxyacalcitriol (OCT) induced maturation and marked expression of CD14 on the cells, but the cells constitutively expressed Toll-like receptor 2 (TLR2) and TLR4 on the cells irrespective of the treatment. PGP induced a high level of interleukin-8 production at doses of 100 ng/ml and higher in OCT-treated THP-1 cells compared with Salmonella LPS, and the production was significantly inhibited by anti-CD14 and anti-TLR2 but not anti-TLR4 antibodies. Consistent with this, TLR2-deficient murine macrophages did not respond to PGP. It was also shown that PGP activity on the THP-1 cells was LPS-binding protein dependent and was inhibited by a synthetic lipid A precursor IV(A). These results indicate that PGP activates monocytic cells in a CD14- and TLR2-dependent manner.

Acidic Glycosphingolipids↗
PubMed2001

Interleukin-18 in human milk.

We analyzed IL-18 levels of human milk. Colostrum contained significantly higher levels of IL-18 compared with early milk and mature milk. By stepwise multiple linear regression analysis, preterm delivery and pregnancy complications of mothers significantly correlated with high levels of IL-18 in human milk (p = 0.0007 and 0.0018, respectively). There was a significant correlation between the levels of IL-18 and soluble Fas ligand in colostrum (p = 0.0003). IL-18 was detected in actively secreting epithelial cells in lactating mammary gland by immunohistochemical staining. These results suggest that IL-18 in colostrum plays an important role in host defense of high-risk neonates.

Base Sequence↗
PubMed2001

[Strain-, sex- and species-related differences of acetohexamide reductase and 20 beta-hydroxysteroid dehydrogenase activities in liver microsomes of experimental animals].

We examined physiological and genetic factors affecting acetohexamide reductase (AHR) and 20 beta-hydroxysteroid dehydrogenase (20 beta-HSD) activities in liver microsomes of experimental animals. Pronounced strain-related differences were found in both activities of AHR and 20 beta-HSD present in liver microsomes of male rats. Among rat strains tested in this study, even though a Wistar-Imamichi (WIM) rat strain was taken to lack AHR activity, it exhibited a significant 20 beta-HSD activity. These findings appeared to be in conflict with our conclusion reported so far, which AHR and 20 beta-HSD present in liver microsomes of male rats are identical enzymes. Thus the reason for this discrepancy was discussed. Furthermore, AHR and 20 beta-HSD activities were little or not observed in liver microsomes of female rats or male experimental animals other than the rat, indicating the existence of sex- and species-related differences in these two enzyme activities.

20-Hydroxysteroid Dehydrogenases↗
PubMed2001

Interleukin-18 in hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is characterized by dysregulated hyperactivation of macrophages and T helper 1 (Th1) cells accompanied by excessive secretion of inflammatory cytokines. Although TNF-alpha and IFN-gamma are known to be important factors for the development of the disease, the mechanism of their overproduction has not been clarified, yet. We measured serum IL-18 levels of patients with HLH to investigate the possible significance of IL-18 in its pathophysiology, especially in IFN-gamma production. IL-18 levels were significantly increased in all patients with HLH compared with healthy controls. A significant correlation was observed between IL-18 and IFN-gamma levels. In addition to IFN-gamma and soluble Fas ligand (sFasL), IL-18 levels significantly correlated with disease activity. IL-18 may play important roles in the pathogenesis of HLH, particularly through induction of Th1 cells. In addition, IL-18 measurement may not only be useful for the diagnosis, but also for the evaluation of disease activity.

Cytokines↗
PubMed2001

Immunoglobulin treatment prevents congestive heart failure in murine encephalomyocarditis viral myocarditis associated with reduction of inflammatory cytokines.

We have previously shown that immunoglobulin therapy suppressed murine coxsackievirus B3 myocarditis. In the present study, we examined the effects of immunoglobulin upon murine myocarditis induced by encephalomyocarditis virus, which is not pathogenic to humans. Antiviral activity of immunoglobulin (Venilon) against encephalomyocarditis virus could not be detected in vitro. The production of cytokines was decreased in virus-infected macrophages by the treatment of immunoglobulin in vitro. Immunoglobulin (1 g/kg/day) was administered intraperitoneally to the virus-infected C3H/He mice daily for 2 weeks, beginning simultaneously with virus inoculation in experiment I and on day 14 after virus inoculation in experiment II. In experiment I, survival rate did not differ significantly between immunoglobulin-treated and untreated groups. In experiment II, survival rate was higher in immunoglobulin compared with control groups. Immunoglobulin administration suppressed the development of myocardial necrosis with T-lymphocyte infiltrates in mice not only in the acute viremic but in the chronic aviremic stages concomitantly associated with the reduction of inflammatory cytokines, i.e., tumor necrosis factor-alpha, interferon-gamma, macrophage inflammatory protein-2, and interleukin-6. Taken together, immunoglobulin therapy could have the potential to prevent congestive heart failure.

Animals↗
PubMed2001

Complement-dependent platelet degradation and anaphylactoid shock in mice induced by lipopolysaccharide carrying the mannose homopolymer.

Intravenous injection of specified bacterial lipopolysaccharides (LPSs) induced anaphylactoid shock in mice of various strains, including LPS-resistant C3H/HeJ. The reaction was accompanied by occasional mortality of mice within 1 h. Prior to shock, rapid accumulation of blood platelets in the lungs and liver followed by degradation of platelets (or release of their contents) and tissue destruction were observed. In this study, LPS specimens carrying mannose-homopolymer (MHP), which markedly activate the human complement system through the lectin pathway, induced marked platelet degradation and anaphylactoid shock in BALB/c mice. In contrast, in C5-deficient DBA/2 mice, the platelet degradation and anaphylactoid reactions did not occur. Anti-complement agent K-76 COOH (C5 inhibitor) protected BALB/c mice from mortality in the anaphylactoid reaction. K-76 COOH also inhibited platelet degradation, but not accumulation, induced by LPS in mice. Based on these findings, we postulated that strong complement activation by specified LPS preparations induced degradation of platelets that have accumulated in the lungs and liver, resulting in acute inflammation accompanied by severe tissue destruction, especially in the lungs, which in turn leads to anaphylactoid reaction.

Anaphylaxis↗
PubMed2000

Epstein-Barr virus (EBV) load and cytokine gene expression in activated T cells of chronic active EBV infection.

To identify the role of T cells in chronic active Epstein-Barr virus (EBV) infection, EBV and cytokine gene expression was quantified by use of real-time polymerase chain reaction (PCR) among 6 patients who fulfilled the diagnostic criteria for chronic active EBV infection. Four of these patients showed clonal expansion of EBV-infected T cells. Quantitative PCR for EBV DNA in peripheral blood of patients with symptomatic chronic active EBV infection showed higher copy numbers of virus (mean, 1.45 x 10(5) copies/mL) than were seen in blood from patients with infectious mononucleosis (3.08 x 10(3) copies/mL) or with EBV-associated hemophagocytosis (2.95 x 10(4) copies/mL). Fractionated CD3(+) HLA-DR(+) cells from patients with chronic active EBV infection contained higher copy numbers than did CD3(+) HLA-DR(-) cells. Quantitative PCR for cytokines revealed that interferon-gamma, interleukin (IL)-2, IL-10, and transforming growth factor-beta genes were expressed at higher levels in HLA-DR(+) than in HLA-DR(-) T cells. These results suggest that activated T cells in chronic active EBV infection expressed high levels of EBV DNA and both Th1 and Th2 cytokines. EBV-infected T cells may contribute to the unbalanced cytokine profiles of chronic mononucleosis.

Adolescent↗
PubMed2000

Cleavage of CD14 on human gingival fibroblasts cocultured with activated neutrophils is mediated by human leukocyte elastase resulting in down-regulation of lipopolysaccharide-induced IL-8 production.

Activated polymorphonuclear leukocytes (PMNs) release various types of proteases and express them on the cell surface. The proteases play important roles in PMN-mediated events. In the present study, flow cytometric analysis revealed that CD14 expression on human gingival fibroblasts (HGF) was markedly reduced by PMA-activated PMNs in a coculture system. We found that this reduction was caused by both secreted and cell surface proteases produced by activated PMNs. A protease responsible for the reduction was found to be human leukocyte elastase (HLE) secreted from the activated PMNs by use of various protease inhibitors, although HLE was only partially involved in CD14 reduction caused by cell-bound molecule(s) on fixed PMNs. Analysis with purified HLE revealed a time- and dose-dependent reduction of CD14 on HGF, and complete reduction was observed by 20 microg/ml HLE treatment for 30-60 min, but the other molecules such as CD26, CD59, CD157, and MHC class I on HGF were only slightly reduced. This reduction of CD14 resulted from direct proteolysis by HLE on the cell surface, because HLE reduced CD14 on fixed HGF and also on purified cell membranes. As a result of CD14 proteolysis, IL-8 production by HGF was suppressed when triggered by 10 ng/ml LPS, but not by IL-1alpha, indicating that HLE inhibited a CD14-dependent cell activation. These findings suggested that activated PMNs have a potential negative feedback mechanism for HGF function at the inflammatory site, particularly in periodontal tissues.

Adolescent↗
PubMed2000

Further studies on 20beta-hydroxysteroid dehydrogenase with carbonyl reductase-like activity present in liver microsomes of male rats.

Further characterizations of 20beta-hydroxysteroid dehydrogenase (20beta-HSD) present in liver microsomes of male rats were examined. A significant relationship was observed between 20beta-HSD and acetohexamide reductase (AHR) activities in liver microsomes of male rats. The hepatic microsomal 20beta-HSD and AHR preferentially required NADPH as a cofactor. When NADPH was replaced by NADH, NADP or NAD at the same concentration, these reductase activities were little detected. The hepatic microsomal 20beta-HSD and AHR activities in streptozotocin-induced diabetic rats were much lower than those in the corresponding controls. The hepatic microsomal 20beta-HSD and AHR activities appeared as one main peak, respectively, on DEAE-Sephacel column chromatography, and the peak of 20beta-HSD activity was in good agreement with that of AHR activity. Based on these results, we conclude that 20beta-HSD present in liver microsomes of male rats functions as AHR, and exhibits a carbonyl reductase-like activity.

Alcohol Oxidoreductases↗
PubMed2000

Proteolysis of human monocyte CD14 by cysteine proteinases (gingipains) from Porphyromonas gingivalis leading to lipopolysaccharide hyporesponsiveness.

Cysteine proteinases (gingipains) elaborated from Porphyromonas gingivalis exhibit enzymatic activities against a broad range of host proteins and are considered key virulence factors in the onset and development of adult periodontitis and host defense evasion. In this study, we examined the ability of arginine-specific gingipains (high molecular mass Arg-specific gingipain (HRGP) and Arg-specific gingipain 2) and lysine-specific gingipain (KGP) to cleave monocyte CD14, the main receptor for bacterial cell surface components such as LPS. Binding of anti-CD14 mAb MY4 to human monocytes was almost completely abolished by 0.3 microM HRGP and KGP treatments for 15 min, and 1 microM RGP2 for 30 min. In contrast, the expressions of Toll-like receptor 4, and CD18, CD54, CD59, and HLA-A, -B, -C on monocytes were slightly increased and decreased, respectively, by 0. 3 microM HRGP and KGP. This down-regulation resulted from direct proteolysis, because 1) gingipains eliminated MY4 binding even to fixed monocytes, and 2) CD14 fragments were detected in the extracellular medium by immunoblot analysis. Human rCD14 was degraded by all three gingipains, which confirmed that CD14 was a substrate for gingipains. TNF-alpha production by monocytes after HRGP and KGP treatments was decreased at 1 ng/ml, but not at 20 microg/ml LPS, indicating that gingipains inhibited a CD14-dependent cell activation. These results suggest that gingipains preferentially cleave monocyte CD14, resulting in attenuation of the cellular recognition of bacteria, and as a consequence sustain chronic inflammation.

Adhesins, Bacterial↗
PubMed2000

Cbfa1, an essential transcription factor for bone formation, is expressed in testis from the same promoter used in bone.

Cbfa1 is an essential transcription factor for bone formation, but its transcripts have also been detected in thymus and testis. To elucidate the expression of Cbfa1 in testis, we isolated Cbfa1 cDNA from mouse testis. First we examined the length of the transcripts expressed in mouse testis by Northern hybridization. Using a cDNA probe that can detect both Type-I and Type-II Cbfa1 (Type-I: originally reported as Pebp2alphaA by Ogawa et al.; Type-II: originally reported as til-1 by Stewart et al.), 1.8-kb transcripts were detected in testis, and larger transcripts (6.3 kb and 7.4 kb) in T-cell lines, thymus and bone. Using a Type-II specific probe (bone isoform-specific probe), surprisingly, 1.8-kb testis transcript(s) were detected as well as those (6.3 kb) found in bone. In addition, the transcription start site in mouse testis coincides with one of three start sites identified in bone. These results suggest that the testis transcript is generated from the same promoter of Type-II Cbfa1, which is thought to be active only in osteoblasts and some chondrocytes. Next, to define the difference in length of transcripts, we isolated the Cbfa1 cDNA from mouse testis. Sequence analysis of the cDNA showed that alternative splicing around exon 2 and poly-adenylation within exon 8 occurred in the testis isoform, which produce the smaller transcripts. These data revealed that testis Cbfa1 mRNA is transcribed from same promoter used in bones, but the post-transcriptional regulation is different between testis and skeletal tissues.

Animals↗
PubMed2000

Catalytic diastereoselective sulfimidation of diaryl sulfides and application of chiral sulfimides to asymmetric allylic alkylation.

The copper-catalyzed diastereoselective imidation of diaryl sulfides bearing a chiral oxazolinyl moiety at the ortho-position with [N-(p-toluenesulfonyl) imino]phenyliodinane (TsN=IPh) or Chloramine-T trihydrate [TsN(Cl)Na.3H2O] was successfully carried out to give the corresponding optically active N-tosylsulfimides in good yields. For example, the imidation of diphenyl sulfide bearing a methoxymethyl moiety at the 4-position of the oxazoline ring with TsN(Cl)Na.3H2O in acetonitrile in the presence of 10 mol% Cu(OTf)2 at 25 degrees C for 24 h affords the corresponding optically active N-tosylsulfimide in 52% isolated yield with a high diastereoselectivity of 99%. Hydrolysis of the optically active N-p-tosylsulfimides converts them into the corresponding optically active sulfimides in high yields without loss of diastereoselectivity. These novel optically active sulfimides and N-tosylsulfimides work as efficient chiral ligands for palladium(II)-catalyzed allylic alkylation of 1, 3-diphenyl-3-acetoxy-1-propene with dimethyl malonate to give the corresponding alkylation product quantitatively and with a high stereoselectivity (up to 90% ee).

Journal Article↗
PubMed2000

Influence of angiotensin-converting enzyme gene polymorphism on development of athlete's heart.

BACKGROUND AND HYPOTHESIS: Genetic influence on development of athlete's heart is uncertain. This study investigated whether angiotensin-converting enzyme (ACE) gene polymorphism influenced development of athlete's heart. METHODS: Forty-three participants in a 100-km ultramarathon were classified on the basis of ACE gene polymorphism into a deletion group (n = 26) and an insertion group (n = 17). Echocardiograms were recorded to determine left ventricular end-diastolic and end-systolic diameters, interventricular septal thickness, left ventricular posterior wall thickness, left ventricular mass, and ejection fraction. RESULTS: Left ventricular end-diastolic diameter (65.5 +/- 4.0 mm) and left ventricular mass (369.5 +/- 73.9 g) were significantly larger in the subjects with deletion than in those with insertion (57.4 +/- 4.2 mm, 306.5 +/- 93.7 g). However, no significant differences in the other parameters were noted. CONCLUSIONS: In long-distance runners, ACE gene polymorphism of the D/D and D/I genotypes has a stronger influence on left ventricular hypertrophy than polymorphism of the I/I genotype.

Adult↗
PubMed2000

Protection against murine coxsackievirus B3 myocarditis by T cell vaccination.

T cell vaccination regulates autoimmunity by the modification of helper and suppressor T cells. The present study was performed to examine whether T cell vaccination can prevent viral myocarditis in vivo. We used coxsackievirus B3 myocarditis in mice as an animal model with the analysis of lymphokine-activated killer cell activity. Vaccination of the mice with T lymphocytes significantly prolonged survival and improved cardiac histology of murine myocarditis. The effects of T cell vaccination were most evident when T cells sensitized with the same virus were used. Vaccination of the mice with T cells from other strains of mice showed lesser protective effects. Clearance of myocardial virus was not affected by this treatment. The efficacy of T cell vaccination was confirmed in vitro by the decrease of the lymphokine-activated killer cell activity against EL-4 tumor cells and cultured myocytes. T cell vaccination of mice prolonged survival and improved myocardial lesions of animals inoculated with coxsackievirus B3.

Animals↗